Potentiation of noise induced threshold shifts and hair cell loss by carbon monoxide

Previous studies have determined that severe systemic hypoxia disrupts cochlear function acutely, but have suggested that augmentation of cochlear perfusion may successfully protect cochlear function under all but the most profound hypoxic treatments. In the current study we report on the chronic effects of simultaneous exposures to noise and carbon monoxide on pure tone thresholds and hair cell survival in rats. Following initial threshold determination, rats received acute exposure to carbon monoxide, noise, or both agents concurrently. Thresholds were evaluated 2-4 and 6-8 weeks later. The data show that carbon monoxide alone does not affect either auditory thresholds or compromise hair cells at the light microscopic level. The noise exposure alone produced variable, but quite limited permanent threshold shifts which were related to the power spectrum of the broad band noise that was employed. Hair cell loss was restricted to the basal turn of the cochlea. Simultaneous exposure to carbon monoxide and noise induced large threshold shifts at all frequencies studied, but the effect was greatest at the highest test frequency; an effect not consistent with the noise power spectrum. Widespread hair cell loss persisted over fully half of the basilar membrane in the most severely affected rat. Outer hair cells appear to be particularly vulnerable. Carbon monoxide plus noise did not appear to preferentially disrupt a particular row of outer hair cells. These data complement existing evidence that hyperoxia can mitigate against noise induced injury and reinforce the view that some types of noise induced damage may result from metabolic insufficiencies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27227/1/0000234.pd

Effects of carbon monoxide on cochlear electrophysiology and blood flow

The belief that the cochlea is particularly vulnerable to a reduction in oxygen availability comes predominantly from studies reporting the disruption of electrophysiological measures, such as the compound action potential, endocochlear potential, inner hair cell intracellular potentials or afferent nerve fiber responses by asphyxiation. Because hypoxia has frequently been suggested as an underlying mechanism by which many ototoxic agents produce injury, and because such agents are not likely to completely disrupt oxygen delivery, we investigated the effects of graded hypoxia (using doses of carbon monoxide) on cochlear blood flow, the compound action potential (CAP) and the cochlear microphonic (CM). High doses of carbon monoxide injected intra-peritoneally yielded reversible loss of the CAP sensitivity for high frequency tone bursts, the extent of which was dose dependent. The loss was observed first at the highest frequency tested (50 kHz) and as carboxyhemoglobin levels increased, contiguous lower frequencies were influenced. Recovery progressed from low to high frequencies as carboxyhemoglobin levels declined. Carbon monoxide administration also produced a dose dependent elevation in the cochlear blood flow measured by a laser Doppler flow monitor. The data suggest that carbon monoxide administration disrupts cochlear function only under extremely severe exposure conditions. An elevation in cochlear blood flow may well serve as a protective mechanism which maintains cochlear function in the face of declining blood oxygen carrying capacity and delivery. While the site of action of carbon monoxide in the cochlea is uncertain, the data clearly indicate that elements involved in the generation of the CAP for high frequency tones are particularly vulnerable. This suggests that such elements may have different metabolic requirements from other lower frequency regions of the cochlea and/or that oxygen delivery (blood circulation) differs in the basal portion of the cochlea.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26857/1/0000422.pd

Trimethyltin ototoxicity: evidence for a cochlear site of injury

The environmental contaminant, trimethyltin (TMT), produces a profound elevation in tone intensity necessary to inhibit the acoustic startle reflex in laboratory animals which recovers over a prolonged period except at very high frequencies. The recovery that is observed does not begin until 3 to 5 weeks after a single acute administration depending upon dosage. As opposed to the very temporary threshold shifts by the salicylates and loop diuretics or the permanent and progressive ototoxicity resulting from aminoglycoside antibiotics the time course for recovery of acoustic startle reflex inhibition after TMT appears to be an anomaly for a chemical ototoxicant. In terms of the duration of loss only, this pattern appears similar to that sometimes observed after noise exposure. The current investigation replicates the finding that recovery of acoustic startle reflex inhibition after TMT is frequency related in that only the highest frequency impairment appears to be permanent. While this frequency dependence suggests a cochlear locus of injury, both the known neurotoxic effects of TMT and the time course of the behavioral impairment suggest a more central locus of injury. Compound action potential and cochlear microphonic recordings made from the round window in the current study confirm a preferential high frequency effect of TMT and demonstrate a significant cochlear component to the ototoxic effects of this agent. ototoxicity, peripheral auditory damage, trimethyltin, reflex modification audiometry, compound action potential, cochlear microphonicPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26388/1/0000475.pd

Acrylonitrile Potentiates Noise-Induced Hearing Loss in Rat

Acrylonitrile, one of the 50 most commonly produced industrial chemicals, has recently been identified as a promoter of noise-induced hearing loss (NIHL). This agent has the potential to produce oxidative stress through multiple pathways. We hypothesize that acrylonitrile potentiates NIHL as a consequence of oxidative stress. The objectives of this study were to characterize acrylonitrile exposure conditions that promote permanent NIHL in rats and determine the ability of this nitrile to produce auditory dysfunction by itself. Additionally, we sought to determine whether a spin-trap agent that can form adducts with ROS would protect against the effects of acrylonitrile. Acrylonitrile administration produced significant elevation in NIHL detected as a loss in compound action potential sensitivity. The effect was particularly robust for high-frequency tones and particularly when acrylonitrile and noise were given on repeated occasions. Acrylonitrile by itself did not disrupt threshold sensitivity. Administration of the spin-trap agent phenyl-N-tert-butylnitrone (PBN), given to rats prior to acrylonitrile and noise, did block the elevation of NIHL by acrylonitrile. However, PBN at the dose and time interval given was ineffective in protecting auditory function in subjects exposed to noise alone. The results suggest that oxidative stress may play a role in the promotion of NIHL by acrylonitrile